cpi-613 in combination with modified folfirinox in patients with locally advanced pancreatic cancer

Conditions: Pancreatic Ductal Adenocarcinoma

Summary: this study is a single arm, phase ii trial, of 45 patients with locally advanced pancreatic ductal adenocarcinoma. the efficacy of the novel drug and mitochondrial inhibitor, cpi-613, in conjunction with standard-of-care folfrinox, as a first-line therapy will be evaluated. pre-treatment, diagnostic biopsy tissue will be collected when available, and clinical data will be evaluated to determine if the combination results in improved overall survival compared to historical experience.

primary objective: 1) to determine if cpi-613 increases overall survival (os) when used in combination with mfolfirinox, in patients with locally advanced pancreatic cancer. secondary (exploratory) objectives: 1. to assess the safety of cpi-613 + mfolfirinox combination in patients with locally advanced pancreatic cancer. 2. to collect tissue specimens for future correlative studies 3. to estimate median progression free survival (pfs) when cpi- 613 is used in combination with mfolfirinox, in patients with locally advanced pancreatic cancer. 4. to estimate the percent resected when cpi-613 is used in combination with mfolfirinox in patients with locally advanced pancreatic cancer

Eligibility criteria:
inclusion criteria: * cytologically confirmed pancreatic adenocarcinoma * locally advanced (including unresectable or borderline resectable) pancreatic cancer based on ct imaging, as determined by the pi * eastern cooperative oncology group (ecog) performance status being 0-1 within 1 week of planned start of therapy. * expected survival \>3 months. * male and female patients 18 to not older than 80 years of age * women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device (iud), oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation. * fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists. * laboratory values ≤2 weeks must be: * adequate hematologic (granulocyte count ≥1500/mm3; white blood cell \[wbc\] ≥3500 cells/mm3; platelet count ≥100,000 cells/mm3; absolute neutrophil count \[anc\] ≥1500 cells/mm3; and hemoglobin ≥9 g/dl). * adequate hepatic function (aspartate aminotransferase \[ast/sgot\] ≤3x upper normal limit \[unl\], alanine aminotransferase \[alt/sgpt\] ≤3x unl, bilirubin ≤1.5x unl). * adequate renal function (serum creatinine ≤2.0 mg/dl or 177 μmol/l). * adequate coagulation ("international normalized ratio" or inr must be \<1.5) unless on therapeutic blood thinners. * no evidence of clinically significant active infection and no serious infection within the past month. * mentally competent, ability to understand and willingness to sign the informed consent form. exclusion criteria: * patients under the age of 18 or older than 80 years of age * endocrine or acinar pancreatic carcinoma * resectable pancreatic cancer * metastatic pancreatic cancer based on imaging * prior surgical or medical treatment for pancreatic cancer * patients receiving any other standard or investigational treatment for their cancer with a primary goal of improving survival within the past 2 weeks prior to initiation of cpi-613 treatment. * serious medical illness that would potentially increase patients' risk for toxicity * any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease). * pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of cpi-613 is unknown). * lactating females. * fertile men unwilling to practice contraceptive methods during the study period. * life expectancy less than 3 months. * any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients. * unwilling or unable to follow protocol requirements. * active including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction. * patients with a history of myocardial infarction that is \<3 months prior to registration. * evidence of active infection, or serious infection within the past month. * patients with known hiv infection. * any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient.